Parental knowledge, attitude and practice regarding paediatric dental trauma. A systematic review.

AIM: Dental trauma is one of the major oral health problems faced during the developmental ages. Most of the traumatic events occur at home; therefore, parents are frequently required to provide appropriate first aid measures. This systematic review aimed to synthesize the available evidence parents have regarding the topic of dental trauma, with a focus on their level of knowledge, attitude, and practice. METHODS: The systematic review was performed according to PRISMA guidelines. The research question was structured using the PICO framework (PROSPERO ID: CRD42023397318). CONCLUSION: Parents' knowledge about dental trauma management is quite limited, and this has a negative impact on the long-term prognosis of traumatised teeth. It is crucial to increase parents' knowledge and awareness about the importance of dental traumas in paediatric age.

[Comprehensive Preoperative Evaluation of Patients with Lung Cancer]. / Umfassende präoperative Evaluation von Patienten mit Lungenkrebs.

Surgical resection continues to be a mainstay of curative treatment of patients with non-small cell lung cancers stages I - III and some small cell lung cancers. Reported rates of complications and mortality vary considerably. Therefore, a thorough and comprehensive preoperative evaluation of lung cancer patients is crucial in order to select appropriate surgical candidates and to determine their individual risk, including the extent of resection possible. Following available data and guidelines, such evaluation should include: ECOG-scoring, cardiac risk assessment, cerebrovascular assessment, pulmonary risk assessment, including split function analysis, and additional initiation or adjustment of treatment where appropriate; in patients aged ≥ 70 years: functional scoring (IADL). Risk stratification results in three groups: patients at low risk for complications and mortality, patients at increased risk, and patients who usually are not candidates for surgical resection. Finally, in order to support autonomous decisions of patients on optimal treatment based on defined risks, physicians must be familiar with values and preferences of patients as well as their familial and social situation.

[Comprehensive Preoperative Evaluation of Patients with Lung Cancer]. / Umfassende präoperative Evaluation von Patienten mit Lungenkrebs.

Surgical resection continues to be a mainstay of curative treatment of patients with non-small cell lung cancers stages I - III and some small cell lung cancers. Reported rates of complications and mortality vary considerably. Therefore, a thorough and comprehensive preoperative evaluation of lung cancer patients is crucial in order to select appropriate surgical candidates and to determine their individual risk, including the extent of resection possible. Following available data and guidelines, such evaluation should include: ECOG-scoring, cardiac risk assessment, cerebrovascular assessment, pulmonary risk assessment, including split function analysis, and additional initiation or adjustment of treatment where appropriate; in patients aged ≥ 70 years: functional scoring (IADL).Risk stratification results in three groups: patients at low risk for complications and mortality, patients at increased risk, and patients who usually are not candidates for surgical resection.Finally, in order to support autonomous decisions of patients on optimal treatment based on defined risks, physicians must be familiar with values and preferences of patients as well as their familial and social situation.

The chaperone-like sodium phenylbutyrate improves factor IX intracellular trafficking and activity impaired by the frequent p.R294Q mutation.

Essentials Missense mutations often impair protein folding, and thus intracellular trafficking and secretion. Cellular models of severe type I hemophilia B were challenged with chaperone-like compounds. Sodium phenylbutyrate improved intracellular trafficking and secretion of the frequent p.R294Q. The increased coagulant activity levels (∼3%) of p.R294Q would ameliorate the bleeding phenotype. SUMMARY: Background Missense mutations often impair protein folding and intracellular processing, which can be improved by small compounds with chaperone-like activity. However, little has been done in coagulopathies, where even modest increases of functional levels could have therapeutic implications. Objectives To rescue the expression of factor IX (FIX) variants affected by missense mutations associated with type I hemophilia B (HB) through chaperone-like compounds. Methods Expression studies of recombinant (r)FIX variants and evaluation of secreted levels (ELISA), intracellular trafficking (immunofluorescence) and activity (coagulant assays) before and after treatment of cells with chaperone-like compounds. Results As a model we chose the most frequent HB mutation (p.R294Q, ~100 patients), compared with other recurrent mutations associated with severe/moderate type I HB. Immunofluorescence studies revealed retention of rFIX variants in the endoplasmic reticulum and negligible localization in the Golgi, thus indicating impaired intracellular trafficking. Consistently, and in agreement with coagulation phenotypes in patients, all missense mutations resulted in impaired secretion (< 1% wild-type rFIX). Sodium phenylbutyrate (NaPBA) quantitatively improved trafficking to the Golgi and dose dependently promoted secretion (from 0.3 ± 0.1% to 1.5 ± 0.3%) only of the rFIX-294Q variant. Noticeably, this variant displayed a specific coagulant activity that was higher (~2.0 fold) than that of wild-type rFIX in all treatment conditions. Importantly, coagulant activity was concurrently increased to levels (3.0 ± 0.9%) that, if achieved in patients, would ameliorate the bleeding phenotype. Conclusions Altogether, our data detail molecular mechanisms underlying type I HB and candidate NaPBA as affordable 'personalized' therapeutics for patients affected by the highly frequent p.R294Q mutation, and with reduced access to substitutive therapy.

Differential functional readthrough over homozygous nonsense mutations contributes to the bleeding phenotype in coagulation factor VII deficiency.

Essentials Potentially null homozygous Factor(F)7 nonsense mutations are associated to variable bleeding symptoms. Readthrough of p.Ser112X (life-threatening) and p.Cys132X (moderate) stop codons was investigated. Readthrough-mediated insertion of wild-type or tolerated residues produce functional proteins. Functional readthrough over homozygous F7 nonsense mutations contributes to the bleeding phenotype. SUMMARY: Background Whereas the rare homozygous nonsense mutations causing factor (F)VII deficiency may predict null conditions that are almost completely incompatible with life, they are associated with appreciable differences in hemorrhagic symptoms. The misrecognition of premature stop codons (readthrough) may account for variable levels of functional full-length proteins. Objectives To experimentally evaluate the basal and drug-induced levels of FVII resulting from the homozygous p.Cys132X and p.Ser112X nonsense mutations that are associated with moderate (132X) or life-threatening (112X) symptoms, and that are predicted to undergo readthrough with (132X) or without (112X) production of wild-type FVII. Methods We transiently expressed recombinant FVII (rFVII) nonsense and missense variants in human embryonic kidney 293 cells, and evaluated secreted FVII protein and functional levels by ELISA, activated FX generation, and coagulation assays. Results The levels of functional FVII produced by p.Cys132X and p.Ser112X mutants (rFVII-132X, 1.1% ± 0.2% of wild-type rFVII; rFVII-112X, 0.5% ± 0.1% of wild-type rFVII) were compatible with the occurrence of spontaneous readthrough, which was magnified by the addition of G418 - up to 12% of the wild-type value for the rFVII-132X nonsense variant. The predicted missense variants arising from readthrough abolished (rFVII-132Trp/Arg) or reduced (rFVII-112Trp/Cys/Arg, 22-45% of wild-type levels) secretion and function. These data suggest that the appreciable rescue of p.Cys132X function was driven by reinsertion of the wild-type residue, whereas the minimal p.Ser112X function was explained by missense changes permitting FVII secretion and function. Conclusions The extent of functional readthrough might explain differences in the bleeding phenotype of patients homozygous for F7 nonsense mutations, and prevent null conditions even for the most readthrough-unfavorable mutations.

PML is required for telomere stability in non-neoplastic human cells.

Telomeres interact with numerous proteins, including components of the shelterin complex, whose alteration, similarly to proliferation-induced telomere shortening, initiates cellular senescence. In tumors, telomere length is maintained by Telomerase activity or by the Alternative Lengthening of Telomeres mechanism, whose hallmark is the telomeric localization of the promyelocytic leukemia (PML) protein. Whether PML contributes to telomeres maintenance in normal cells is unknown. We show that in normal human fibroblasts the PML protein associates with few telomeres, preferentially when they are damaged. Proliferation-induced telomere attrition or their damage due to alteration of the shelterin complex enhances the telomeric localization of PML, which is increased in human T-lymphocytes derived from patients genetically deficient in telomerase. In normal fibroblasts, PML depletion induces telomere damage, nuclear and chromosomal abnormalities, and senescence. Expression of the leukemia protein PML/RARα in hematopoietic progenitors displaces PML from telomeres and induces telomere shortening in the bone marrow of pre-leukemic mice. Our work provides a novel view of the physiologic function of PML, which participates in telomeres surveillance in normal cells. Our data further imply that a diminished PML function may contribute to cell senescence, genomic instability, and tumorigenesis.

The -308 TNFα and the -174 IL-6 promoter polymorphisms associate with effective anti-TNFα treatment in seronegative spondyloarthritis.

The genetic predisposition to a long-term efficacy of anti-tumor necrosis factor (TNF)α treatment in seronegative spondyloarthritis (SpA) was investigated by analysing the possible correlation between several single nucleotide gene polymorphisms and the retention rate of anti-TNFα therapies. We compared patients needing to switch the first anti-TNFα (Sw, No. 64) within at least 12 months of follow-up with patients not needing to switch (NSw, No. 123), observing at least 6 months of treatment to establish anti-TNFα failure, leading to treatment change. Response to treatment was evaluated by standardised criteria (BASDAI for axial involvement, DAS28-EULAR for peripheral involvement). The TNFα -308 A allele and the interleukin (IL)-6 -174GG homozygosis resulted as independent biomarkers predicting survival of the first anti-TNFα therapy in SpA patients (P=0.007, odds ratio (OR): 4.4, 95% confidence interval (CI)=1.5-13.1 and P=0.035, OR: 2.1, 95% CI=1.1-4.4). Also, the male gender (P=0.001, OR: 3.4, 95% CI=1.6-7.1) associated with the NSw phenotype, whereas no association was found either with the specific diagnosis or the predominant joint involvement.

Diabetes outcomes within integrated healthcare management programs.

AIM: The aim of this observational study was to assess mortality of patients with type 2 diabetes by type of healthcare delivery system, i.e. through specialist centers or generalist doctors, or integrated care. METHODS: The study was conducted at the "Vicentino Ovest" Local Health District in the Veneto Region (north-eastern Italy) from January 1, 2008 to December 31, 2010. Patients with diabetes (≥ 20 years old) were identified using different public health databases. They were grouped as: patients followed up by specialists at diabetes clinics (DS); patients seen only by their own general practitioner (GP); and patients receiving integrated care (DS-GP). Cox's regression analysis was used to estimate adjusted hazard ratios for available potential predictors of death by level of care. RESULTS: The crude mortality rate was highest in the GP group (26.1 per 1000 person-years), the difference being minimal when compared with the DS group (21.7 per 1000 person-years) and more marked when compared with the DS-GP group (8.8 per 1000 person-years). Patients followed up by their GPs had a 2.7 adjusted RR for mortality by comparison with the DS-GP group. CONCLUSIONS: The findings of the present study could demonstrate that it is safe and cost-effective, after a first specialist assessment at a diabetes service, for low-risk diabetic patients to be managed by family physicians as part of a coordinated care approach, based on the specialist's clinical recommendations; GPs can subsequently refer patients to a specialist whenever warranted by their clinical condition.

Occult hepatitis B virus infection among blood donors from the Brazilian Amazon: implications for transfusion policy.

BACKGROUND: Brazil requires the performance of both a test for hepatitis B surface antigen (HBsAg) and a test for antibodies to the core of hepatitis B for blood donor screening. Blood centres in regions of high HBV endemicity struggle to maintain adequate stocks in face of the high discard rates due to anti-HBc reactivity. We evaluated the potential infectivity of donations positive for anti-HBc in search of a rational approach for the handling of these collections. STUDY DESIGN AND METHODS: We tested anti-HBc reactive blood donations from the state of Amazonas for the presence of HBV DNA and for titres of anti-HBs. The study population consists of village-based donors from the interior of Amazonas state. RESULTS: Among 3600 donations, 799 were anti-HBc reactive (22·2%). We were able to perform real-time PCR for the HBV S gene on specimens from 291 of these donors. Eight of these samples were negative for HBsAg and positive for HBV DNA and were defined as occult B virus infections (2·7%). Six of those eight specimens had anti-HBs titres above 100 mIU/ml, indicating the concomitant presence of the virus with high antibody titres. CONCLUSION: A small proportion of anti-HBc reactive donors carry HBV DNA and anti-HBs testing is not useful for predicting viremia on them. This finding indicates the possibility of HBV transmission from asymptomatic donors, especially in areas of high HBV prevalence. Sensitive HBV DNA nucleic acid testing may provide another level of safety, allowing eventual use of anti-HBc reactive units in critical situations.

Técnica de rives-stoppa en las eventraciones de la línea media: prescindencia de la fijación perimetral de la malla / Rives-Stoppa repair without mesh fixation for midline incisional hernias: long term follow up

Objetivo: La Técnica de Rives-Stoppa para las eventraciones de la línea media instala una malla retro rectal fijada en sus bordes con puntos percutáneos. Se han propuesto otras formas de fijación y en este estudio prescindimos de ella. Material y Método: El presente estudio observacional, descriptivo, prospectivo, se realizó en pacientes intervenidos consecutivamente entre los años 1995 y 2002. Se usó anestesia epidural con sedación profunda. Se usó la técnica estándar de Rives-Stoppa prescindiendo de la fijación perimetral. Los pacientes deambularon y se dieron de alta precozmente. Resultados: Se da cuenta de la evolución postoperatoria de 64 pacientes, 48 mujeres y 16 varones con una edad promedio de 58,9 (26-85) años. El 25 por ciento era hipertenso, el 9,3 por ciento diabético y el 80,2 por ciento obeso con un IMC > 30. La hospitalización promedio fue de 3,9 (2-16) días. Hubo 4 infecciones superficiales, un trombo embolismo pulmonar, un íleo abdominal prolongado y dos infecciones pulmonares. El seguimiento a largo plazo pudo realizarse en 48 pacientes (75 por ciento) comprobándose 5 recidivas (10,4 por ciento), ubicadas en el borde dista o proximal de la reparación herniaria, y 13,2 por ciento de dolor crónico moderado. A pesar de la recurrencia, el 97 por ciento de los pacientes se manifestó satisfecho o muy satisfecho con el tratamiento. Discusión: Los resultados son comparables con los dados a conocer con fijación de la malla. La modificación técnica propuesta disminuye el tiempo quirúrgico y el riego de infección y de neuralgia post operatoria. Para una ulterior disminución de las recidivas debe aumentarse el solapamiento cefálico y caudal de la malla.

Background: The Rives-Stoppa technique for midline incisional hernias places a Mersilene mesh in the retro rectal space, which is kept in place with transcutaneous sutures. Other forms of fixation have been proposed. Aim: To assess the long term results of the surgical technique without fixation of the mesh. Material and Methods: An observational, descriptive, prospective study performed in 64 patients aged 26 to 85 years (48 women) consecutively operated between 1995 and 2002. The standard Rives-Stoppa technique was used, except for the usage of a Prolene mesh without fixation. Ambulation was started on the first postoperative day and patients were discharged after removal of drains. Results: Eighty percent of patients were obese, 25% had high blood pressure and 9% were diabetic. Patients were discharged at a median of four (range two-16) days after surgery. Four superficial infections, one case of thromboembolic disease, one case of prolonged ileus and two pulmonary infections were recorded as complications. A long term follow-up was carried out in 48 patients (75%). Five patients had small recurrences (10%), localized at the cephalic or caudal borders of the mesh, and six patients (13%) reported slight abdominal pain. In spite of recurrences, 97% of patients were satisfied or very satisfied with the treatment. Conclusions: These results are similar to those obtained using mesh fixation. Increasing distal and proximal mesh overlap should enhance these results.

X chromosome gene methylation in peripheral lymphocytes from monozygotic twins discordant for scleroderma.

Scleroderma (SSc) is a rare connective tissue disease characterized by fibrosis, microvasculopathy and autoimmune features. The role of genetics is limited in SSc, as suggested by similar concordance rates in monozygotic and dizygotic twin pairs, while environmental factors may act through epigenetic changes, as demonstrated for specific genes. Further, sex chromosome changes have been reported in SSc and may explain the female preponderance. In the present study we compared the methylation profile of all X chromosome genes in peripheral blood mononuclear cells from monozygotic twins discordant (n=7) and concordant (n=1) for SSc. Methylated DNA immunoprecipitations from each discordant twin pair were hybridized to a custom-designed array included 998 sites encompassing promoters of all X chromosome genes and randomly chosen autosomal genes. Biostatistical tools identified sites with an elevated probability to be consistently hypermethylated (n=18) or hypomethylated (n=25) in affected twins. Identified genes include transcription factors (ARX, HSFX1, ZBED1, ZNF41) and surface antigens (IL1RAPL2, PGRMC1), and pathway analysis suggests their involvement in cell proliferation (PGK1, SMS, UTP14A, SSR4), apoptosis (MTM1), inflammation (ARAF) and oxidative stress (ENOX2). In conclusion, we propose that X chromosome genes with different methylation profiles in monozygotic twin pairs may constitute candidates for SSc susceptibility.

Study on the possible role of the -174G>C IL-6 promoter polymorphism in predicting response to rituximab in rheumatoid arthritis.

OBJECTIVE: Identification of genetic biomarkers of response to biologics in rheumatoid arthritis (RA) is a relevant issue. The -174G>C interleukin-6 (IL-6) promoter polymorphism was investigated in RA patients treated with rituximab (RTX), being IL-6 a key cytokine for B cell survival and proliferation, thus possibly implicated in rituximab efficacy. METHODS: The study was conducted in a real-life retrospective cohort of 142 unselected RA patients (120F/22M) treated with RTX and referred to 7 rheumatologic centres in the north of Italy. One hundred and thirteen (79.6%) patients were rheumatoid factor (RF)-positive and 112 (78.9%) were anti-CCP antibodies positive. The response to therapy was evaluated at the end of the sixth month after the first RTX infusion, by using both the EULAR criteria (DAS28) and the ACR criteria. The IL-6 -174G>C promoter polymorphism was analyzed by RFLP following previously reported methods. RESULTS: Lack of response to RTX at month +6 by EULAR criteria was more prevalent in RA patients with the IL-6 -174 CC genotypes (9/21, 42.8%), than in the GC/GG patients (23/121, 19.0%) (OR 3.196, 95% CI=1.204-8.485; p=0.0234). Similar results were found when evaluating the response by ACR criteria. No differences were found in RA duration, baseline DAS28, baseline HAQ, RF status, anti-CCP status according to the different IL-6 -174 genotypes. CONCLUSION: IL-6 promoter genotyping may be useful to better plan treatment with RTX in RA. Larger replication studies are in course to confirm these preliminary results.

[Rheumatoid factor positivity rather than anti-CCP positivity, a lower disability and a lower number of anti-TNFalpha agents failed are associated with response to rituximab in rheumatoid arthritis]. / La presenza del fattore reumatoide, la disabilità ed il numero di precedenti anti-TNFalpha falliti predicono la risposta clinica a rituximab nell'artrite reumatoide.

OBJECTIVE: Predictors of response to biologics in rheumatoid arthritis (RA) is an important issue in the current era. Rituximab (RTX) has been demonstrated effective and safe in active RA, resistant to traditional or biologic DMARDs. METHODS: Fifty-seven patients with active longstanding RA were treated with RTX after traditional DMARD or anti-TNF alpha therapy failure. RESULTS: Number of anti-TNF treatment previously failed (p=0.005), HAQ (p=0.013), rheumatoid factor (RF) (p=0.0002) and anti-CCP (p=0.006) were associated with an ACR response > or =50 at the end of 6th month by univariate analysis. Multivariate analysis confirmed that the number of anti-TNF previously failed, baseline HAQ and RF, but not anti-CCP were associated with an ACR response > or =50. EULAR moderate/good response was associated with ESR value (p=0.036), HAQ (p=0.032), and RF (p=0.01) by univariate analysis, while only RF positivity was associated with EULAR moderate/good response by multivariate analysis. CONCLUSIONS: RF positivity rather than anti-CCP positivity is a predictor of response to RTX, suggesting that RF-positive patients with low disability may obtain a clinical response when treated to RTX after the first anti-TNF agent failure or after traditional DMARD therapies. Larger studies are required to confirm these results.

Eventraciones: reconstitución plástica de la línea alba mediante doble sutura invaginante isotensional (DSII) / Reconstruction of midline incisional hernias using a double isotensional suture

Background: Incisional hernias of the midline are frequently multisacular and its treatment without a mesh is followed by a high rate of recurrences. Aim: To report a new technique for the treatment of midline incisional hernias, performing an isotensional suture of the midline with Vycril® 2-0, followed by a double invaginant suture of the rectus aponeurosis with Ethybond® 2-0. Material and Methods: Observational prospective study of 90 women and 26 men, aged 54 +/- 13 and 59 +/- 13 years respectively, with a hernia sac smaller than 15 cm and with an aponeurotic defect smaller than 3 cm, operated between January 2002 and December 2005. Results: Surgery was performed under local anesthesia on an ambulatory basis. The surgical procedure consisted in the excision of a skin lozenge which included the scar, dissection and reduction of all sacs and isotensional suture of the midline with Vycryl #1®. This suture was followed by a double invaginating suture of the rectus sheath in the midline with Ethylon® 0. Five superficial infections and two hematomas were observed. Seven recurrences (7 percent) in 99 patients (85 percent of the sample), were found during a mean follow up of 4.6 years (range 2-6). Conclusions: The double invaginating isotensional suture (DIIS) is an acceptable alternative for the treatment of small and middle size incisional hernias of the midline.

Las eventrorrafias sin malla de la línea media se asocian con una elevada tasa de recidivas. En esta publicación damos cuenta de una técnica fascial utihzable en eventraciones peque±as y medianas de la línea media que hemos llamado doble sutura invaginante isotensional (DSII). El estudio observacional descriptivo es una serie clínica constituida por 90 mujeres con una edad promedio de 54 +/- 12,9 años y 26 varones con una edad promedio de 59 +/- 13,7 años, intervenidos entre el Iº de Enero de 2002 y el 31 de Diciembre de 2005. En 14 casos se trató de una eventración recidivada. Se intervinieron pacientes con un saco de hasta 15 cm, único o múltiple, con un anillo inferior a 3 cm, con una edad fisiológica inferior a los 70 años y ASA 1 y 2. La obesidad y la diabetes mellitus no constituyeron una contraindicación. La operación se efectuó con anestesia local, en forma ambulatoria en 98 y con anestesia raquídea en 18 casos. La técnica incluyó resección de un losanjo de piel, manejo de los sacos y rrafia mediante sutura de la línea alba con Vycryl® 2-0, seguida de doble sutura invaginante del plano aponeurótico con Ethybond® 0. Apreciamos 5 infecciones y 2 hematomas de la herida. Un seguimiento promedio de 4,6 (2 - 6) años se efectuó en 99 pacientes (85 por ciento) de la muestra, apreciándose 7 recidivas (7 por ciento). La DSII es una técnica alternativa en las eventraciones pequeñas y medianas de la línea media.

[Recycle of jute bags; asbestos in agriculture, exposure and pathology ]. / Riciclaggio di sacchi di juta, patologie asbesto-correlate ed esposizione ad amianto in agricoltura.

During the last four years, a deeper examination of malignant mesothelioma (MM) cases occurred within non asbestos textile industry highlighted asbestos past exposure in several textile industrial divisions. In spite of that, poor information about recycled textile bags previously containing asbestos fibres is available to the National Mesothelioma Registry, although holding a remarkable data bank on more than 3500 work histories and sources of asbestos exposures. Besides the analysis of the exposure circumstances and the registered health effects of the past exposure within the recycling activity, the aim of this research was to relate the possible involvement of the agricultural sector, where the use of recycled jute bags was very diffused. The MM cases were collected from the Mesothelioma Registry of Brescia, asbestosis, pleural plaques and lung cancer cases were collected from the Occupational Diseases Archive of the Local Public Occupational Health Service of the Province of Brescia. During the 1977-2006 period, 8 cases of MM, 4 cases of pulmonary asbestosis, 4 of isolated bilateral pleural plaques and I of lung cancer in pulmonary asbestosis, were observed among workers employed in bags recycling activity in 4 small companies, one of them still operating, employing about 50 workers. Even more, among the 65 MM cases classified by the Registry with "unknown asbestos exposure" (UAE), the most relevant frequency of working histories concerned the agriculture sector. Confirming a past signalling, the investigations underlined the cross linkage between this working activity and the diffusion of recycled bags in the agriculture sector. In the Province of Brescia, the activities of these small jute bags recycling plants were linked, even geographically, to the asbestos cement manufacture plant using a huge number of bags, roughly until mid seventies. Therefore, a large number of these recycled bags, previously containing asbestos, were generally used for harvesting and trading agricultural typical products of northern Italy. According to the 2003 National Mesothelioma Registry Guide Lines, MM in agricultural workers are still classified as UAE due to poor information available. In the light of these new findings, it looks reasonable to review the UAE within agriculturalists attributing a new classification of "possible" occupational asbestos exposure, although other exposure circumstances might have occurred in the past.

Friedreich's ataxia: clinical heterogeneity in two sisters.

Diagnostic evaluation of two sisters affected by ataxia, with similar age of onset, revealed a characteristic trinucleotide expansion in the Friedreich's ataxia (FRDA) locus and two different phenotypic presentations. At onset the elder sister had retained deep tendon reflexes (FARR), while the younger sister presented classic FRDA. The GAA expansion in the patients' alleles proved to be similar in both siblings, ruling out that age at onset and clinical heterogeneity could be due to different FRDA mutations. On the whole, clinical and genetic data on these patients confirmed that FARR is a variant phenotype of FRDA.

[Duodenal gastrointestinal stromal tumors. Report of a case]. / Tumores estromales gastrointestinales duodenales.

Gastrointestinal stromal tumors (GIST) are lesions whose diagnosis and treatment have varied in the last decade. We report a 76 year-old male with a history of eight episodes of upper gastrointestinal bleeding. A duodenography showed an elevated lesion in the third portion of the duodenum with a central ulceration. It was initially managed with tumorectomy and primary closure of the duodenum. The pathological study of the surgical specimen revealed a low grade gastrointestinal stromal tumor. Three years later, the tumor recurred and pancreatoduodenectomy was performed. Due to the high risk of malignant potential, tumor size, number of mitoses and the presence of necrosis, imatinib mesylate was started. The patient had a satisfactory evolution, without evidences of recurrence after 15 months of follow up.